Vesicle trafficking of neurotransmitters, neuronal response to nitric oxide, and SOCaE are critical functions in neurons. The InsP3-R may be a crucial regulator of these processes (see sec 30b). Binding partners of the InsP3-R that we identify may modulate such regulation. Recent work in this field has demonstrated that the InsP3-R is a central entity in many Ca2+ signaling pathways in neuronal systems. Identification of the microenvironment of proteins in which the InsP3-R resides will further our knowledge of InsP3-R, and its binding partners involvement within in neuronal signaling pathways. Additionally it will increase our knowledge of how the InsP3-R is able to discriminate between the many pathways that converge on its activity. The main objective of this proposal is to examine the role of the InsP3-R and InsP3-R signaling pathways in neurons. Specifically I intend to identify binding partners for the InsP3-R, and examine their roles in neurotransmitter secretion, SOCaE, and regulation of the InsP3-R itself.